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Oxidative stress is one of the major mechanisms implicated in endotoxin-induced acute lung injury. Seabuckthorn paste (SP), a traditional Tibetan medicine with high content of polyphenols and remarkable antioxidant activity, is commonly used in treating pulmonary diseases. In the present study, the protective effects and possible underlying mechanisms of SP on lipopolysaccharide- (LPS-) induced acute lung injury in mice were investigated. It was found that body weight loss, lung tissue microstructure lesions, transvascular leakage increase, malondialdehyde augmentation, and the reduction of superoxide dismutase and glutathione peroxidase levels caused by LPS challenge were all consistently relieved by SP treatment in a dose-dependent manner. Moreover, accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in lung nuclei caused by SP treatment was observed. Our study demonstrated that SP can provide significant protection against LPS-induced acute lung injury through maintaining redox homeostasis, and its mechanism involves Nrf2 nuclear translocation and activation.

• A simultaneous microwave/ultrasonic-assisted enzymatic extraction method was established for the first time. • Simultaneous microwave/ultrasonic-assisted enzymatic process can improve antioxidant capacity of juice by-product extract. • Simultaneous microwave/ultrasonic-assisted enzymatic process can increase the extraction efficiency of antioxidant ingredients. • <b>Nitraria tangutorun</b> Bobr. juice by-products extract exhibited excellent cell protection effect from oxidative injury.<br>By-products originating from food processing are a considerable disposal problem for the food industry. Because of the absence of specifically effective processing technology, huge quantities of by-products are often abandoned as rubbish and prone to microbial spoilage. Given this, a simultaneous microwave/ultrasonic assisted enzymatic extraction (SMU-AEE) method was established for the first time, and performed for antioxidant ingredients extraction from <b>Nitraria tangutorum</b> juice by-products (NJB) in the present study. Its experimental conditions were optimized by single factor test and response surface methodology (RSM), and gave the corresponding response values for antioxidant capacity of NJB extract (NJBE) of 219.73 ± 7.03 mg TE/g, which was 27.62%-190.23% higher than those obtained by traditional extraction methods. Chemical composition assay suggested that the increasing of antioxidant capacity of NJBE by SMU-AEE was because of the improvement of extraction efficiency of antioxidant ingredients from NJB, including phenols, flavonoids and anthocyanins. Furthermore, oxidative injury protection ability assay showed that NJBE was good at protecting cells from UVB-oxidative phototoxicity and doxorubicin-oxidative cardiotoxicity, and its protecting ability surpasses or approaches to that of grape seed extract (GSE, the positive control drug), indicating its good potential to be a natural antioxidant in food and pharmaceutical industries.

Graphical abstract Highlights • The anti-hyperuricemia effects and active components of the traditional Tibetan medicine formula TFTS were investigated. • Total 106 compontents were identified or characterized in TFTS by UHPLC-Q-TOF-MS/MS. • It was summarized the diagnostic ion and neutral loss patterns of MS/MS cracking of tannic compounds. Abstract TongFengTangSan (TFTS), a traditional Tibetan medicine comprising of Tinospora sinensis (TS), Terminalia chebula Retz (TC) and Trogopterori faeces (TF), is used to treat joint diseases like gout, gout arthritis, swelling, pain etc. Despite the significant therapeutic effects of TFTS, its pharmacological components have not been analyzed so far. Therefore, the chemical composition of the effective part of TFTS was analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). The results show that the ethanol extract (EE) of TFTS was more effective in reducing the serum uric acid (SUA) and XOD (Serum and Liver) levels in a hyperuricemic rats model compared to the TFTS raw powder (RP). UHPLC-Q-TOF-MS/MS identified a total of 106 compounds in the positive and negative ion mode, of which 87 were from TC, 13 from TS and 6 from TF. In addition, 106 compounds contained 57 tannins, 6 triterpenoids, 10 alkaloids, 7 flavonoids, 22 organic acids and 4 phenylpropanoids. The preliminary results indicate that the EE of TFTS includes the active anti hyperuricemic substances. The present study first investigated the efficacy and the active components of TFTS in hyperuricemic treatment, and further summarized the diagnostic ion and neutral loss patterns of MS/MS cracking of tannic compounds. These findings lay the foundation for the further study and clinical application of TFTS. [ABSTRACT FROM AUTHOR]

Four common traditional tibetan medicine prescription preparations "Anzhijinghuasan, Dangzuo, Renqingchangjue and Rannasangpei" in tibetan areas were selected as study objects in the present study. The purpose was to try to establish a kind of wet digestion and flow injection-hydride generation-atomic absorption spectrometry (FI-HAAS) associated analysis method for the content determinations of lead and arsenic in traditional tibetan medicine under optimized digestion and measurement conditions and determine their contents accurately. Under these optimum operating conditions, experimental results were as follows. The detection limits for lead and arsenic were 0.067 and 0.012 µg · mL(-1) respectively. The quantification limits for lead and arsenic were 0.22 and 0.041 µg · mL(-1) respectively. The linear ranges for lead and arsenic were 25-1,600 ng · mL(-1) (r = 0.9995) and 12.5-800 ng · mL(-1) (r = 0.9994) respectively. The degrees of precision(RSD) for lead and arsenic were 2.0% and 3.2% respectively. The recovery rates for lead and arsenic were 98.00%-99.98% and 96.67%-99.87% respectively. The content determination results of lead and arsenic in four traditional tibetan medicine prescription preparations were as fol- lows. The contents of lead and arsenic in Anzhijinghuasan are 0.63-0.67 µg · g(-1) and 0.32-0.33 µg · g(-1) in Anzhijinghua- san, 42.92-43.36 µg · g(-1) and 24.67-25.87 µg · g(-1) in Dangzuo, 1,611. 39-1,631.36 µg · g(-1) and 926.76-956.52 µg- g(-1) in Renqing Changjue, and 1,102.28-1,119.127 µg-g(-1) and 509.96-516.87 µg · g(-1) in Rannasangpei, respectively. This study established a method for content determination of lead and arsenic in traditional tibetan medicine, and determined the content levels of lead and arsenic in four tibetan medicine-prescription preparations accurately. In addition, these results also provide the basis for the safe and effective use of those medicines in clinic.

OBJECTIVE: To study the heat processing technics of Nanhanshuishi.METHOD: To find the best processing technic, the single factor experiments and orthogonal experiments were designed basing on the processing technics summarized by consulting documents, scriptures and investigating some Tibetan hospitals, meanwhile, the content of Ca, Fe, Mn, Zn, and Cu in the processed Nanhanshuishi in single factor experiments and orthogonal experiments were detected. RESULT: The best processing technic of Nanhanshuishi was as follows: Nanhanshuishi was crashed to 10-20 mm in diameter, the ratio of the weight of Aconiti Kusnezoffii Radix and potassium nitrate was 1: 2, and the boiling time was 3 h. CONCLUSION: The work in this article provided a basic processing technic data for clarifying the mechanism of processing and establishing the perfect processing technics of Nanhanshuishi.

Zuotai (gTso thal) is a typical representative of Tibetan medicines containing heavy metals, but there is still lack of modem safety evaluation data so far. In this study, acute toxicity test, sub-acute toxicity test, one-time administration mercury distribution experiment, long-term mercury accumulative toxicity experiment and preliminary study on clinical safety of Compound Dangzuo were conducted in the hope of obtain the medicinal safety data of Zuotai. In the acute toxicity test, half of KM mice given the lethal dose of Zuotai were not died or poisoned, and LD50 was not found. The maximum tolerated dose of Zuotai was 80 g x kg(-1). In the subacute toxicity test, Zuotai could reduce ALT, AST, Crea levels in serums under low dose (13.34 mg x kg(-1) x d(-1)) and medium dose (53.36 mg x kg(-1) x d(-1)), with significant difference under low dose, and increase the levels of ALT, AST, MDA, Crea in serums under high dose (2 000 mg x kg(-1) x d(-1)); besides, the levels of BUN and GSH in serums reduced with the increase in dose of Zuotai, indicating a significant dose-effect relationship. In the one-time administration distribution experiment, the content of mercury in rat kidney, liver and lung increased after the one-time administration with Zuotai, with a significant dose-dependent relationship in kidney. In the long-term mercury accumulative toxicity experiment, KM mice were administered with equivalent doses of Zuotai for 4.5 months and then stopped drug administration for 1.5 months. Since the 2.5th month, they showed significant mercury accumulation in kidney, which gradually reduced after drug withdrawal, without significant change in mercury content in liver, spleen and brain and ALT, AST, TBIL, BUN and Crea in serum. At the 4.5th month after drug administration, KM mice showed slight structural changes in kidney, liver and spleen tissues, and gradually recovered to normal after drug withdrawal. Besides, no significant difference in weight gain was found between the Zuotai group and the control group. According to the findings of the clinical safety study of Dangzuo, after subjects administered Dangzuo under clinical dose for one month, their serum biochemical indicators, blood routine indicators and urine routine indicators showed no significant adverse change. This study proved that traditional Tibetan medicine Zuotai was slightly toxic, with a better safety in clinical combined administration and no adverse effects on bodies under the clinical dose and clinical medication cycle. However, long-term high-dose administration of Zuotai may have a certain effect on kidney.;

The objective of the present study is to research the herb of Swertia mussotii Franch and its different extracts by tristep infrared spectroscopy. The main constitute of Swertia mussotii Franch-gentiamarin, which is also the higher content constitute, was selected as the control components to analyze the infrared spectroscopy and second derivative infrared spectroscopy of different extracts of Swertia mussotii Franch, at the same time, the different concentration of ethanol extracts were also analyzed by two-dimensional correlation spectroscopy (2D-COS). The results indicated that the intensity of 1 611 and 1 075 cm(-1) of gentiamarin, which are its two main absorptions in the infrared spectra, has the positive correlation with the content change in different extracts. The infrared spectroscopy of extracts are similar if the polarity of extract solvents is close; with the decreases in solution polarity, the intensity of 2 853, 1 733, 1 464, 1 277 and 1 161 cm(-1) in infrared spectroscopy of different extracts is increased, the content of esters and the extraction percentage terpenoid compounds are also increased; the different concentration of ethanol extracts has obviously difference when they are analyzed by two-dimensional correlation spectroscopy (2D-COS). The positive correlation between the intensity of absorptions and the content of the gentiamarin indicates that the infrared spectroscopy can reflect the content change in constitute; the similar and the change trend of the different concentrations of ethanol extract infrared spectroscopy approve the scientificalness of decoction of traditional medicine; infrared spectroscopy that used in the research can be used as an accurate, rapid and effective method in the pharmacological activity tests of transitional herbal Swertia mussotii F. and it's different extracts, even in the research on the tibetan medicine.

Zuotai is composed mainly of β-HgS, while cinnabar mainly contains α-HgS. Both forms of HgS are used in traditional medicines and their safety is of concern. This study aimed to compare the hepatotoxicity potential of Zuotai and α-HgS with mercury chloride (HgCl2) and methylmercury (MeHg) in mice. Mice were orally administrated with Zuotai (30 mg/kg), α-HgS (HgS, 30 mg/kg), HgCl2 (33.6 mg/kg), or CH3HgCl (3.1 mg/kg) for 7 days, and liver injury and gene expressions related to toxicity, inflammation and Nrf2 were examined. Animal body weights were decreased by HgCl2 and to a less extent by MeHg. HgCl2 and MeHg produced spotted hepatocyte swelling and inflammation, while such lesions are mild in Zuotai and HgS-treated mice. Liver Hg contents reached 45-70 ng/mg in HgCl2 and MeHg groups; but only 1-2 ng/mg in Zuotai and HgS groups. HgCl2 and MeHg increased the expression of liver injury biomarker genes metallothionein-1 (MT-1) and heme oxygenase-1 (HO-1); the inflammation biomarkers early growth response gene (Egr1), glutathione S-transferase (Gst-mu), chemokine (mKC) and microphage inflammatory protein (MIP-2), while these changes were insignificant in Zuotai and HgS groups. However, all mercury compounds were able to increase the Nrf2 pathway genesNAD(P)H: quinone oxidoreductase 1 (Nqo1) and Glutamate-cysteine ligase, catalytic subunit (Gclc). In conclusion, the Tibetan medicine Zuotai and HgS are less hepatotoxic than HgCl2 and MeHg, and differ from HgCl2 and MeHg in hepatic Hg accumulation and toxicological responses.

UNLABELLED: Zuotai is composed mainly of β-HgS, while cinnabar mainly contains α-HgS. Both forms of HgS are used in traditional medicines and their safety is of concern. This study aimed to compare the hepatotoxicity potential of Zuotai and α-HgS with mercury chloride (HgCl2) and methylmercury (MeHg) in mice. Mice were orally administrated with Zuotai (30 mg/kg), α-HgS (HgS, 30 mg/kg), HgCl2 (33.6 mg/kg), or CH3HgCl (3.1 mg/kg) for 7 days, and liver injury and gene expressions related to toxicity, inflammation and Nrf2 were examined. Animal body weights were decreased by HgCl2 and to a less extent by MeHg. HgCl2 and MeHg produced spotted hepatocyte swelling and inflammation, while such lesions are mild in Zuotai and HgS-treated mice. Liver Hg contents reached 45-70 ng/mg in HgCl2 and MeHg groups; but only 1-2 ng/mg in Zuotai and HgS groups. HgCl2 and MeHg increased the expression of liver injury biomarker genes metallothionein-1 (MT-1) and heme oxygenase-1 (HO-1); the inflammation biomarkers early growth response gene (Egr1), glutathione S-transferase (Gst-mu), chemokine (mKC) and microphage inflammatory protein (MIP-2), while these changes were insignificant in Zuotai and HgS groups. However, all mercury compounds were able to increase the Nrf2 pathway genes NAD(P)H: quinone oxidoreductase 1 (Nqo1) and Glutamate-cysteine ligase, catalytic subunit (Gclc). In conclusion, the Tibetan medicine Zuotai and HgS are less hepatotoxic than HgCl2 and MeHg, and differ from HgCl2 and MeHg in hepatic Hg accumulation and toxicological responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum tanguticum has been widely used as a remedy for infectious diseases in traditional Tibetan medicine in China. The total alkaloids of Aconitum tanguticum (TAA) are the main active components of Aconitum tanguticum and have been demonstrated to be effective in suppressing inflammation. Our aim was to investigate the protective effects of TAA on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats.MATERIALS AND METHODS: TAA was extracted in 95% ethanol and purified in chloroform. After vacuum drying, the TAA powder was dissolved in dimethyl sulfoxide. Adult male Sprague-Dawley rats were randomly divided into six groups. Rats were given dexamethasone (DXM, 4 mg/kg) or TAA (60 mg/kg, 30 mg/kg) before LPS injection. The PaO2and PaO2/FiO2 values, lung wet/dry (W/D) weight ratio and histological changes in lung tissue were measured. The cell counts, protein concentration, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF), and myeloperoxidase (MPO) activity in lung tissue were determined at 6, 12 or 24 h after LPS treatment. In addition, the NF-κ B activation in lung tissue was analyzed by western blot. RESULTS: In ALI rats, TAA significantly reduced the lung W/D ratio and increased the value of PaO2 or PaO2/FiO2 at 6, 12 or 24 h after LPS challenge. TAA also reduced the total protein concentration and the number of total cells, neutrophils or lymphocytes in BALF. In addition, TAA decreased MPO activity in the lung and attenuated histological changes in the lung. Furthermore, TAA inhibited the concentration of TNF-α, IL-6 and IL-1β in BALF at 6, 12 or 24 h after LPS treatment. Further study demonstrated that TAA significantly inhibited NF-κ B activation in lung tissue. CONCLUSIONS: The current study proved that TAA exhibited a potent protective effect on LPS-induced ALI in rats through its anti-inflammatory activity.

Abstract Ethnopharmacological relevance Tibetan medicine has been practiced for 3800 years. Anzhijinhua San (AZJHS), which is a traditional Tibetan medicine, has been effective in the treatment of indigestion, anorexia and cold diarrhea. However, the effects of AZJHS on allergic diarrhea have not been reported. Aim of the study The aim of the present study was to elucidate the effect of AZJHS on experimental ovalbumin-induced diarrhea and elucidate its possible mechanism. Materials and methods Female BALB/c mice were sensitized by intraperitoneal injection with 50 μg ovalbumin (OVA) and 1 mg alum in saline twice during a 2-week period. From day 28, mice were orally challenged with OVA (50 mg) every other day for a total of ten times. AZJHS (46.8 and 468.0 mg/kg) was orally administered every other day from day 0–46. Food allergy symptoms were evaluated. OVA- specific IgE, 5-HT and its metabolites in serum were determined. Immunohistochemical and histopathology were performed in gastrointestinal tract tissues. 5-HT-related gene expression was assayed in the colon. Results Severe symptoms of allergic diarrhea were observed in the model group (diarrhea, anaphylactic response, and rectal temperature). AZJHS (46.8 and 468.0 mg/kg) significantly reduced mouse diarrhea and significantly prevented the increases in OVA-specific IgE levels (P < 0.05), which challenge with OVA. AZJHS (46.8 and 468.0 mg/kg) significantly prevented the increases in 5-HT-positive cells. The nuclei of EC cells in the AZJHS (46.8 and 468.0 mg/kg) group increased in size and the secretory granules were fewer in number compared with those in the model group. AZJHS (46.8 and 468.0 mg/kg) significantly increased the relative fold changes of 5-HTP and 5-HT compared with the model group. The mRNA expression of the serotonin transporter (Sert) and serotonin receptor 3A (Htr3a) was significantly decreased after the 10th challenge with OVA, and AZJHS (46.8 and 468.0 mg/kg) significantly increased these levels. Conclusions We demonstrated that the administration of AZJHS attenuated OVA-induced diarrhea by regulating the serotonin pathway. These results indicated that AZJHS may be a potential candidate as an anti-allergic diarrhea agent. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

This paper is in order to discussion with the composition and characteristics of Tibetan medicine plant resources, and promote the reasonable protection and utilization of the resources of Tibetan materia medica. Statistical analysis of species, distributions, and others of Chinese endemic seed plant from Tibetan medicine plants and usually used in the clinic of Tibetan medicine. The results showed that there are 523 species (25%) of Chinese endemic seed plant, belonging to 65 families and 162 genera, in about 2 000 varieties of Tibetan medicine plants recorded in relevant literatures. There are 180 Chinese endemic seed plant species (28%) belonging to 42 families and 72 genera from 625 medicine plants usually used in the clinic of Tibetan medicine. Specifically, the most of these Chinese endemic seed plant species are characteristic crude drug used in Tibetan medicine, and mainly or only distributed in Qinghai-Tibet Plateau. And a few species of them were intersected with traditional Chinese medicines (TCM) and other ethnic medicines. In addition, about 10% are listed in China Species Red List. The Qinghai-Tibet Plateau is the most abundant areas of Areal-types of the Chinese endemic seed plant. This is the biological and ecological reason formation the characteristics of Tibetan medicine plant resources. Therefore, strengthen the research of Chinese endemic seed plants used in Tibetan medicine is great significance for the reasonable protection and utilization of Tibetan medicine plant resources.

Bioassay-guided fractionation of the ethanol extract of the aerial parts of Clematis tangutica led to the isolation of two new antifungal triterpene saponins. Their structures were determined to be 3- O-alpha- L-arabinopyranosyl hederagenin 28- O-alpha- L-rhamnopyranosyl ester ( 1) and 3- O-beta- D-glucopyranosyl-(1--> 4)-alpha- L-arabinopyranosyl hederagenin 28- O-alpha- L-rhamnopyranosyl ester ( 2) on the basis of spectral data and chemical evidence. Inhibitory activities of the two saponins against seven fungal strains were evaluated. Compounds 1 and 2 showed evident antifungal activity (MIA approximately 2.5 micrograms/disc) against Saccharomyces cerevisiae, similar to the positive control amphotericin B and ordinary activities (MIA approximately 10 micrograms/disc) against Penicillium avellaneum UC-4376, Candida glabrata, Trichosporon beigelii and Pyricularia oryzae. Compound 2 is a better antifungal agent than compound 1 against most of the fungal strains that were tested.;

Two new polyhydroxy polyacetylenes, herpecaudenes A and B (1 and 2), were isolated from the ethanol extract of fruits of Herpetospermum caudigerum, an important Tibetan medicine. The structures of them were elucidated on the basis of extensive spectroscopic methods including UV, IR, HRESIMS, 1H and 13C NMR, HMBC, HSQC, and 1H-1H COSY. Compound 2 showed significant inhibitory effects on NO production in LPS-activated RAW 264.7 macrophages with IC50 values of 7.05 ± 1.59 µM.

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